How Blood Clots - or Not

Blood thinners keep blood from thickening - coagulating, or clotting. But what’s the difference between one blood thinner and another? To answer that, we have to know a little about how blood clots. More than a dozen clotting factors are involved, each activating the next in an elaborate cascade. Fortunately we don’t have to know all the details - just a few.

A blood clot has two main parts: special blood cells called platelets, and a fibrous substance called, well, fibrin.

When the lining of a blood vessel breaks, material leaks into the blood from behind it - including factors that activate the platelets to clump together to plug the break. The activated platelets also release other clotting factors that make more platelets join in.

Aspirin inactivates cyclooxygenase - COX for short. COX is a factor in pain and inflammation (which is why aspirin is used to treat pain), but platelets need it to produce thromboxane - an important clotting factor. Aspirin inhibits clotting by acting as an antiplatelet drug.

Other antiplatelet drugs, with names ending in –grel like clopidogrel (marketed as Plavix), interfere with receptors for another platelet factor, ADP.

Coagulation is the process of solidifying the plug to form a clot. Factors leaking from just under the blood vessel lining activate substances in the blood, which activate other substances, etc., activating prothrombin to become thrombin. Other substances from injured tissue outside the blood vessel similarly cause prothrombin to become thrombin. Thrombin activates fibrinogen to make fibrin, which binds the platelets together.

Anticoagulant drugs interfere with fibrin formation. Warfarin (marketed as Coumadin) interferes with the action of Vitamin K, which is needed at several stages in the formation of the fibrin mesh. Heparin (used in hospitals) is different; it activates antithrombin III, one of several agents that slow the formation of fibrin.

To make clots go away as the injury heals, the clotting process binds a factor called plasminogen into the clot, and the injured blood vessel gradually releases an agent called tissue plasminogen activator (tPA). The tPA converts the plasminogen to plasmin, which breaks up the fibrin in the clot.

Used as a thrombolytic drug - a “clot-buster” - tPA is commonly administered to stroke and heart attack patients to dissolve the clots blocking their arteries.